HIV-1 (human immunodeficiency virus-1) infection remains a major medical problem, with an estimated 42 million people infected worldwide at the end of 2002. The number of cases of HIV and AIDS (acquired immunodeficiency syndrome) has risen rapidly. In 2002, approximately 5.0 million new infections were reported, and 3.1 million people died from AIDS. Currently available drugs for the treatment of HIV include nucleoside reverse transcriptase (RT) inhibitors or approved single pill combinations: zidovudine (or AZT or Retrovir®), didanosine (or Videx®), stavudine (or Zerit®), lamivudine (or 3TC or Epivir®), zalcitabine (or DDC or Hivid®), abacavir succinate (or Ziagen®), Tenofovir disoproxil fumarate salt (or Viread®), emtricitabine (or FTC), Combivir® (contains −3TC plus AZT), Trizivir® (contains abacavir, lamivudine, and zidovudine), Epzicom® (contains abacavir and lamivudine), Truvada® (contains Viread® and emtricitabine); non-nucleoside reverse transcriptase inhibitors: nevirapine (or Viramune®), delavirdine (or Rescriptor®) and efavirenz (or Sustiva®), and peptidomimetic protease inhibitors or approved formulations: saquinavir, indinavir, ritonavir, nelfinavir, amprenavir, lopinavir, and Kaletra®(lopinavir and Ritonavir). Each of these drugs can only transiently restrain viral replication if used alone. However, when used in combination, these drugs have a profound effect on viremia and disease progression. In fact, significant reductions in death rates among AIDS patients have been recently documented as a consequence of the widespread application of combination therapy. However, despite these impressive results, 30 to 50% of patients ultimately fail combination drug therapies. Insufficient drug potency, non-compliance, restricted tissue penetration and drug-specific limitations within certain cell types (e.g. most nucleoside analogs cannot be phosphorylated in resting cells) may account for the incomplete suppression of sensitive viruses. Furthermore, the high replication rate and rapid turnover of HIV-1 combined with the frequent incorporation of mutations, leads to the appearance of drug-resistant variants and treatment failures when sub-optimal drug concentrations are present. Therefore, novel anti-HIV agents exhibiting distinct resistance patterns, and favorable pharmacokinetic as well as safety profiles are needed to provide more treatment options. Improved HIV fusion inhibitors and HIV entry coreceptor antagonists are two examples of new classes of anti-HIV agents currently being studied by a number of investigators.
The properties of a class of HIV entry inhibitors called HIV attachment inhibitors has been improved in an effort to obtain compounds with maximized utility and efficacy as antiviral agents. A disclosure describing indoles of which the structure shown below for BMS-705 is representative has been disclosed [Antiviral Indoleoxoacetyl Piperazine Derivatives. Wade Blair; Millind Deshpande; Haiquan Fang; Ping-Fang Lin; Tim Spencer; Owen Wallace; Hui Wang; Tao Wang; Zhongxing Zhang and Kap-Sun Yeung WO-00076521 (U.S. Pat. No. 6,469,006 issued), 2000].

Two other compounds, referred to in the literature as BMS-806 and BMS-043 have been described in both the academic and patent art:
                (1) A small molecule HIV-1 inhibitor that targets the HIV-1 envelope and inhibits CD4 receptor binding (Lin, Pin-Fang; Blair, Wade; Wang, Tao; Spicer, Timothy; Guo, Qi; Zhou, Nannan; Gong, Yi-Fei; Wang, H.-G. Heidi; Rose, Ronald; Yamanaka, Gregory; Robinson, Brett; Li, Chang-Ben; Fridell, Robert; Deminie, Carol; Demers, Gwendeline; Yang, Zheng; Zadjura, Lisa; Meanwell, Nicholas; and Colonno, Richard. Proceedings of the National Academy of Sciences of the United States of America (2003), 100(19), 11013-11018);        (2) Biochemical and genetic characterizations of a novel human immunodeficiency virus type 1 inhibitor that blocks gp120-CD4 interactions (Guo, Qi; Ho, Hsu-Tso; Dicker, Ira; Fan, Li; Zhou, Nannan; Friborg, Jacques; Wang, Tao; McAuliffe, Brian V.; Wang, Hwei-gene Heidi; Rose, Ronald E.; Fang, Hua; Scarnati, Helen T.; Langley, David R.; Meanwell, Nicholas A.; Abraham, Ralph; Colonno, Richard J.; and Lin, Pin-fang. Journal of Virology (2003), 77(19), 10528-10536);        (3) Method using small heterocyclic compounds for treating HIV infection by preventing interaction of CD4 and gp120 (Ho, Hsu-Tso; Dalterio, Richard A.; Guo, Qi; and Lin, Pin-Fang. PCT Int. Appl. (2003), WO 2003072028 A2);        (4) Antiviral Azaindole Derivatives Useful for the Treatment of HIV Infection (Wang, Tao; Wallace, Owen; Zhang, Zhongxing; Meanwell, Nicolas A.; and Bender, John A. WO-00162255 (corresponding to U.S. Pat. Nos. 6,476,034 and 6,900,323), 2001);        (5) Method using small heterocyclic compounds for treating HIV infection by preventing interaction of CD4 and gp120. (Ho, Hsu-Tso; Dalterio, Richard A.; Guo, Qi; and Lin, Pin-Fang. PCT Int. Appl. (2003), WO 2003072028A2); and        (6) Discovery of 4-benzoyl-1-[(4-methoxy-1H-pyrrolo[2,3-b]pyridin-3-yl)oxoacetyl]-2-(R)-methylpiperazine (BMS-378806): A Novel HIV-1 Attachment Inhibitor That Interferes with CD4-gp120 Interactions. (Wang, Tao; Zhang, Zhongxing; Wallace, Owen B.; Deshpande, Milind; Fang, Haiquan; Yang, Zheng; Zadjura, Lisa M.; Tweedie, Donald L.; Huang, Stella; Zhao, Fang; Ranadive, Sunanda; Robinson, Brett S.; Gong, Yi-Fei; Ricarrdi, Keith; Spicer, Timothy P.; Deminie, Carol; Rose, Ronald; Wang, Hwei-Gene Heidi; Blair, Wade S.; Shi, Pei-Yong; Lin, Pin-fang; Colonno, Richard J.; and Meanwell, Nicholas A. Journal of Medicinal Chemistry (2003), 46(20), 4236-4239).        
Some description of their properties in human clinical trials have been disclosed (“Antiviral Activity, Safety, and Tolerability of a Novel, Oral Small-Molecule HIV-1 Attachment Inhibitor, IVa, in HIV-1-Infected Subjects” G. Hanna, J. Lalezari, J. Hellinger, D. Wohl, T. Masterson, W. Fiske, J. Kadow, P-F. Lin, M. Giordano, R. Colonno, D. Grasela. Abstract J-32, Feb. 11, 2004, 11th Conference on Retroviruses and Opportunistic Infections (CROI), San Francisco, Calif.).
It should be noted that in all three of these structures, a piperazine amide (In these three structures a piperazine phenyl amide) is present and this group is directly attached to an oxoacetyl moiety. The oxoacetyl group is attached at the 3-position of 4-Fluoro indole in BMS-705 and to the 3 position of substituted azaindoles in BMS-806 and BMS-043.
In an effort to obtain improved anti-HIV compounds, later publications described in part, modifed substitution patterns on the indoles and azaindoles:                (1) Novel Substituted Indoleoxoacetic Piperazine Derivatives Useful for treating HIV Infection and AIDS. (Wallace, Owen B.; Wang, Tao; Yang, Kap-Sun; Pearce, Bradley; Meanwell, Nicholas A.; Qiu, Zhilei; Fang, Haiquan; Xue, Qiufen May and Yin, Zhiwei. WO-00204440 (corresponding to U.S. Pat. No. 6,573,262 & U.S. Pat. No. 6,632,819));        (2) Preparation and antiviral activity of substituted piperazinyloxoacetylindole derivatives. (Wallace, Owen B.; Wang, Tao; Yeung, Kap-Sun; Pearce, Bradley C.; Meanwell, Nicholas A.; Qiu, Zhilei; Fang, Haiquan; Xue, Qiufen May; Yin, Zhiwei. U.S. Pat. Appl. Publ. 2003069245);        (3) Composition and Antiviral Activity of Substituted Azaindoleoxoacetic Piperazine Derivatives. (Wang, Tao; Zhang, Zhongxing; Meanwell, Nicholas A.; Kadow, John F.; and Yin, Zhiwei. WO-02062423);        (4) Composition and antiviral activity of substituted azaindoleoxoacetic piperazine derivatives. (Wang, Tao; Zhang, Zhongxing; Meanwell, Nicholas A.; Kadow, John F.; Yin, Zhiwei; and Xue, Qiufen May. U.S. Pat. Appl. Publ. 20030207910); and        (5) Composition and antiviral activity of substituted azaindoleoxoacetic piperazine derivatives. (Wang, Tao; Zhang, Zhongxing; Meanwell, Nicholas A.; Kadow, John F.; Yin, Zhiwei; Xue, Qiufen May; Regueiro-Ren, Alicia; Matiskella, John D.; Ueda, Yasutsugu. U.S. Pat. Appl. Publ. 2004110785).        
Replacement of these groups with other heteraromatics or substituted heteroaroamatics or bicyclic hydrocarbons was also shown to be feasible:                (1) Indole, Azaindole and Related Heterocyclic Amidopiperazine Derivatives. Wang, Tao; Wallace, Owen B.; Meanwell, Nicholas A.; Zhang, Zhongxing; Bender, John A.; and Kadow, John F. WO-02085301 (corresponding to U.S. Pat. No. 6,825,201);        (2) Bicyclo 4.4.0 Antiviral Derivatives. (Wang, Tao; Wallace, Owen B.; Meanwell, Nicholas A.; Kadow, John F.; Zhang, Zhongxing; and Yang, Zhong. WO-03092695); and        (3) A preparation of diazaindole derivatives, useful as antiviral agents. (Bender, John A.; Yang, Zhong; Kadow, John F.; and Meanwell, Nicholas A. US2005124623).        
A select few replacements for the piperazine amide portion of the molecules have also been described in the art and among these examples are
(A) Piperidine Alkenes:                (1) Indole, Azaindole and Related Heterocyclic 4-Alkenyl Piperidine Amides. (Wang, Tao; Kadow, John F.; Meanwell, Nicholas A.; Zhang, Zhongxing; Yin, Zhiwei; Yeung, Kap-Sun; Qiu, Zhilei; Deon, Daniel H.; James, Clint A.; Ruedinger, Edward H., and Bachand, Carol. US-2004/0063744); and        (2) Preparation and pharmaceutical compositions of indole, azaindole and related heterocyclic 4-alkenyl piperidine amides. (Wang, Tao; Kadow, John F.; Meanwell, Nicholas A.; Yeung, Kap-Sun; Zhang, Zhongxing; Yin, Zhiwei; Qiu, Zhilei; Deon, Daniel H.; James, Clint A.; Ruediger, Edward H.; and Bachand, Carol. U.S. Pat. Appl. 2004/0186292).        
(B) Certain Pyrrolidine Amides:                Indole, Azaindole and Related Heterocyclic Pyrrolidine Derivatives. (Kadow, John F.; Xu, Qiufen; Wang, Tao; Zhang, Zhongxing; and Meanwell, Nicholas A. WO-03068221, 2003.);        
(C) N-aryl or Heteroaryl Piperazines:                Preparation of (aza)indolyloxoacetylpiperazines as anti-HIV drugs (Yeung, Kap-Sun; Farkas, Michelle; Kadow, John F.; Meanwell, Nicholas A.; Taylor, Malcolm; Johnston, David; Coulter, Thomas Stephen; Wright, J. J. Kim. WO-2005004801, 2005.);        
(D) Piperazinyl Ureas:                (1) Preparation of indolyl-, azaindolyl-, and related heterocyclic sulfonylureidopiperazines for treatment of HIV and AIDS. (Kadow, John F.; Regueiro-Ren, Alicia; Xue, Qiufen May. WO-2004000210, 2003); and        (2) Preparation of indolyl-, azaindolyl-, and related heterocyclic ureido and thioureido piperazines for treatment of HIV and AIDS. (Regueiro-Ren, Alicia; Xue, Qiufen May; Kadow, John F.; and Taylor, Malcolm. WO-2004011425, 2004).        
A method for preparing prodrugs was also disclosed in this class (Prodrugs of Piperazine and Substituted Piperidine Antiviral Agents. (Ueda et al., U.S. non-provisional application Ser. No. 11/066,745, filed Feb. 25, 2005).
A publication on new compounds in this class of attachment inhibitors (Jinsong Wang et. al. Org. Biol. Chem. 2005, 3, 1781-1786.) and a patent application on some more remotely related compounds have appeared WO2005/016344 published on Feb. 24, 2005.
Nothing in these references can be construed to disclose or suggest the novel compounds of-this disclosure and their use to inhibit HIV infection.